Kr. Irvine et al., CYTOKINE ENHANCEMENT OF DNA IMMUNIZATION LEADS TO EFFECTIVE TREATMENTOF ESTABLISHED PULMONARY METASTASES, The Journal of immunology, 156(1), 1996, pp. 238-245
DNA immunization can result in the induction of Ag-specific cellular a
nd humoral immune responses and in protective immunity in several Ag s
ystems. To evaluate the utility of DNA-based immunization as a potenti
al cancer treatment strategy, we employed an experimental murine tumor
, CT26, expressing the model tumor-associated Ag, beta-galactosidase (
beta-gal), designated CT26,CL25. A plasmid expressing beta-gal (pCMV/b
eta-gal) administered by particle-mediated gene delivery to the epider
mis using a hand-held, helium-driven ''gene gun'' induced beta-gal-spe
cific Ab and lytic responses. Immunization with this construct prevent
ed the growth of pulmonary metastatic tumor, and the adoptive transfer
of splenocytes generated by pCMV/beta-gal in vivo immunization and cu
ltured in vitro with the beta-gal(876-884) immunodominant peptide redu
ced the number of established pulmonary nodules. DNA immunization alon
e had little or no impact on the growth of established lung metastases
. To enhance the function of DNA immunization for active immunotherapy
, a panel of cytokines was added as adjuvants following DNA administra
tion, Significant reduction in the number of established metastases wa
s observed when human rlL-2, mouse rlL-6, human rIL-7, or mouse rlL-12
were given after DNA inoculation; mouse rlL-12 as an adjuvant had the
most profound effect. These findings suggest that the cytokines invol
ved in the activation and expansion of lymphocyte populations may impr
ove the therapeutic effects of DNA immunization. Given the ease with w
hich plasmid DNA can be prepared to high purity for safe use in humans
with infectious diseases and cancers, DNA immunization administered t
ogether with cytokine adjuvant may be an attractive alternative to rec
ombinant viral vaccines.